Molecular Characteristics of Choledochal Cysts in Children: Transcriptome Sequencing.

Yong Lv,Lihui Pu,Xiaolong Xie,Chengbo Ai,Yi Liu,Qi Wang,Jing Chen,Bo Xiang,Siyu Pu

doi:10.3389/fgene.2021.709340

Yong Lv, Lihui Pu + Show 7 more

Open Access

https://doi.org/10.3389/fgene.2021.709340

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Abstract

A choledochal cyst (CC) is a common congenital biliary disease in children, yet the underlying molecular bases for the cystic and fusiform clinical subtypes are unknown. RNA sequencing (RNA-seq) has been performed on 22 high-quality CC samples, including 12 cystic CC and 10 fusiform CC samples, to search for molecular features. Weighted gene co-expression network analysis (WGCNA) was performed to identify key modules associated with clinical subtypes. Bioinformatic analyses were conducted to elucidate potential mechanisms. Then, we constructed protein–protein interaction (PPI) networks to identify candidate hub genes related to CC. Finally, we used the support vector machine (SVM) to eliminate redundant features and screen out the hub genes. The selected gene expression was determined in CC patients through quantitative real-time polymerase chain reaction (PCR). A total of 6,463 genes were found to be aberrantly expressed between cystic CC and fusiform CC. Twelve co-expression modules that correlated with clinical subtypes of CC were identified and assigned representative colors. Among the 12 modules, the blue module was considered the key module. Two functionally distinct sets of dysregulated genes have been identified in two major subtypes, metabolism-related genes in cystic CC and immune-related genes in fusiform CC. A total of 20 candidate hub genes that were correlated with clinical subtypes were found in the blue module. In addition, we found ERBB2 and WNT11 that have not been studied in CC and verified their differential expression in CC through quantitative real-time PCR experiments. For the first time, we have described the transcriptome characteristics of CC. These results suggest that cystic CC and fusiform CC have different molecular mechanisms. The bi-omics-identified novel candidate genes and pathways might be helpful for personalized treatment and are of great clinical significance for CC.

Highlights

A choledochal cyst (CC), known as congenital biliary dilatation (CBD), is a common congenital biliary disease in children characterized by dilatation of extrahepatic biliary tract
The results showed that the correlation coefficient between gene significance (GS) for CC subtype and MM was highest in the blue module (Figure 4B); that is, the blue module was the most positively correlated with CC subtype, which was consistent with the above findings
Treatment of CCs depends upon the type of cyst (Pastor et al, 2021)

Summary

Introduction

A choledochal cyst (CC), known as congenital biliary dilatation (CBD), is a common congenital biliary disease in children characterized by dilatation of extrahepatic biliary tract. The etiology of CC is unknown, which may be related to an anomalous pancreaticobiliary junction, bile duct dysplasia, and other factors (Friedmacher et al, 2019) These theories cannot explain the pathogenesis of all types of CCs. There are obvious differences in epidemiology, imaging, and clinical features among different types of CCs. CCs were divided into five types in 1977 by Todani et al (1977). Todani’s type II and type III pathologies were rare in children, and type V was Caroli disease that requires a different management. It fails to provide a surgical guideline specific to the subtypes (Makin and Davenport, 2012). At present, dividing CCs into two types (cystic and fusiform extrahepatic dilatation) is the most widespread classification method, which has great advantages in clinical diagnosis and treatment (Diao et al, 2011)

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